title: Platelet endothelial cell adhesion molecule 1 deficiency misguides venous thrombus resolution.
abstract: Platelet endothelial cell adhesion molecule 1 (PECAM-1) is involved in leukocyte migration and angiogenesis, which are key components of venous thrombus resolution. This study investigated the effect of PECAM-1 deficiency on thrombus resolution in FVB/n mice and the extent to which levels of soluble PECAM-1 (sPECAM-1) correlate with delayed thrombus resolution in humans after acute symptomatic deep vein thrombosis (DVT). In a mouse stagnant flow venous thrombosis model Pecam-1(-/-) thrombi were larger, persisted for longer periods of time, and displayed attenuated macrophage invasion and decreased vessel formation in the presence of increased fibrosis. In humans, higher levels of truncated plasma sPECAM-1 possibly cleaved from cell surfaces, were found in patients with delayed thrombus resolution (assessed via duplex-based thrombus scoring) relative to those whose thrombi resolved (median, 25th/75th percentile): 92.5 (87.7/103.4) ng/mL vs 71.5 (51.1/81.0) ng/mL; P < .001. Furthermore, unresolved human deep vein thrombus specimens stained positively with antibodies specific for the extracellular, but not the cytoplasmic domain of PECAM-1, consistent with accumulation of cleaved PECAM-1. Our data suggest a regulatory role of PECAM-1 in venous thrombus resolution and suggest a predictive value of sPECAM-1 for postthrombotic syndrome (PTS) after acute DVT.
authors.affiliation: Department of Internal Medicine I, Elisabethinen Hospital, Linz, Austria;
authors.forename: Joerg
authors.initials: J
authors.lastname: Kellermair
authors.forename: Bassam
authors.initials: B
authors.lastname: Redwan
authors.forename: Sherin
authors.initials: S
authors.lastname: Alias
authors.forename: Joerg
authors.initials: J
authors.lastname: Jabkowski
authors.forename: Adelheid
authors.initials: A
authors.lastname: Panzenboeck
authors.forename: Lukas
authors.initials: L
authors.lastname: Kellermair
authors.forename: Max P
authors.initials: MP
authors.lastname: Winter
authors.forename: Ansgar
authors.initials: A
authors.lastname: Weltermann
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
mesh_terms: D000368:Aged; D000818:Animals; D002465:Cell Movement; D005260:Female; D005342:Fibrinolysis / Q000502:physiology; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood* / Q000235:genetics; D054070:Postthrombotic Syndrome / Q000097:blood* / Q000235:genetics / Q000473:pathology; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D014680:Veins / Q000378:metabolism* / Q000473:pathology; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics / Q000473:pathology
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1